Continuous process for manufacture of lactide polymers with controlled optical purity

ABSTRACT

A process for the continuous production of polylactide polymers from lactic acid which incorporates removal of water or a solvent carrier to concentrate the lactic acid feed followed by polymerization to a low-molecular-weight prepolymer. This prepolymer is fed to a reactor in which a catalyst is added to facilitate generation of lactide, the depolymerization product of polylactic acid. The lactide generated is continuously fed to a distillation system as a liquid or vapor wherein water and other impurities are removed. The resultant purified liquid lactide is fed directly to a polymerization process.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is continuation application of U.S. patentapplication Ser. No. 07/825,059 filed Jan. 24, 1992, now issued as U.S.Pat. No. 5,142,023.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to processes for the continuous productionof lactide polymers from crude lactic acid in the field of biodegradablepolymers.

2. Description of the Prior Art

The continued depletion of landfill space and the problems associatedwith incineration of waste have led to the need for development of trulybiodegradable polymers to be utilized as substitutes fornon-biodegradable or partially biodegradable, petrochemical-basedpolymers. The use of lactic acid and lactide to manufacture abiodegradable polymer is well known in the medical industry. Asdisclosed by Nieuwenhuis et al. (U.S. Pat. No. 5,053,485), such polymershave been used for making biodegradable sutures, clamps, bone plates andbiologically active controlled release devices. It will be appreciatedthat processes developed for the manufacture of polymers to be utilizedin the medical industry have incorporated techniques which respond tothe need for high purity and biocompatibility in the final polymerproduct. Furthermore, the processes were designed to produce smallvolumes of high dollar-value products, with less emphasis onmanufacturing cost and yield. It is believed that prior to Applicants'development, viable, cost-competitive processes for the continuousmanufacture of lactide polymers from lactic acid having physicalproperties suitable for replacing present petrochemical-based polymersin packaging, paper coating and other non-medical industry applicationswere unknown.

It is known that lactic acid undergoes a condensation reaction to formpolylactic acid when water is removed by evaporation or other means. Theoverall polymerization reaction is represented by: ##STR1## While step nof said polymerization reaction is represented by: ##STR2##

As Dorough (U.S. Pat. No. 1,995,970) recognized and disclosed, theresulting polylactic acid is limited to a low molecular weight polymerof limited value, based on physical properties, due to a competingdepolymerization reaction in which the cyclic dimer of lactic acid,lactide, is generated. As the polylactic acid chain lengthens, thepolymerization reaction rate decelerates until it reaches the rate ofthe depolymerization reaction, which effectively limits the molecularweight of the resulting polymers. An example of this equilibriumreaction is represented below. ##STR3##

Given this understanding, Dorough was convinced that high molecularweight polymers could not be generated directly from lactic acid. Hewas, however, successful in generating high molecular weight polymersfrom lactide, through the lactic acid dimer generated from the lowmolecular weight polymers of lactic acid. Because these polymers aregenerated from lactide, they are known as polylactides.

It is well known that lactic acid exists in two forms which are opticalenantiomers, designated as D-lactic acid and L-lactic acid. EitherD-lactic acid, L-lactic acid or mixtures thereof may be polymerized toform an intermediate molecular weight polylactic acid which, uponfurther polymerization, generates lactide as earlier disclosed. Thelactide, or the cyclic dimer of lactic acid, may have one of three typesof optical activity depending on whether it consists of two L-lacticacid molecules, two D-lactic acid molecules or an L-lactic acid moleculeand a D-lactic acid molecule combined to form the dimer. These threedimers are designated L-lactide, D-lactide and meso-lactide,respectively. In addition, a 50/50 mixture of L-lactide and D-lactidewith a melting point of about 126° C. is often referred to in theliterature as D,L-lactide.

DeVries (U.S. Pat. No. 4,797,468) recently disclosed a process for themanufacture of lactide polymers utilizing a solvent extraction processto purify lactide prior to polymerization. With DeVries, disclosure, theinventor recognized that existing literature recommends purification oflactide by several recrystallization steps. It is believed thatprocesses prior to DeVries solvent extraction method, have generallyutilized a recrystallization step to purify the crude lactide in orderto obtain a source of lactide suitable for polymerization. However,processes utilizing such recrystallization steps are known to haverelatively poor yields due to significant losses of lactide during therecrystallization steps. It is believed that producers ofmedical-related biodegradable products have not been concerned with suchlow yields because of the high margin generally expected for sales ofsuch products and the lack of competitive alternatives. It will beappreciated, however, that in developing a process for the large-scale,commercial manufacture of biodegradable polymers, such as polylactides,for use in nonmedical-products-oriented applications where such polymerswill necessarily compete with low-cost polymers made frompetrochemicals, it will be important to maximize yield and minimizeother overall cost factors to produce a biodegradable polymer which iscost-competitive.

The biogradable polylactide polymers must also possess physicalproperties suitable for application in non-medical products presentlyutilizing petrochemical-based polymers such as packaging materials,paper coatings and any other disposable articles. Nieuwenhuis et al.disclose that lactide polymers derived from polymerization of mixturesof the three lactides result in polymers with a variety of usefulphysical properties, including improved biodegradability. However, nocommercially viable process for the large-scale manufacture of suchlactide polymers is believed to have been disclosed to date.

Lactic acid is commercially available and manufactured from severalknown processes. Representative examples of such processes are disclosedby Glassner et al. (European Patent Application, EP 393818, Oct. 24,1990), G Machell, "Production and Applications of Lactic Acid",Industrial Chemist and Chemical Manufacturer, v. 35, pp. 283-90 (1959)and Kirk Othmer, Encyclopedia of Chemical Technology, "Lactic Acid", v.12, pp. 177-78 (2nd ed. 1963).

The optical activity of either lactic acid or lactide is known to alterunder certain conditions, with a tendency toward equilibrium at opticalinactivity, where equal amounts of the D and L enantiomers are present.Relative concentrations of D and L in the starting materials, thepresence of impurities or catalysts and time at varying temperatures andpressures are known to affect the rate of such racemization.

Muller (U.S. Pat. No. 5,053,522) discloses that the preparation ofoptically pure lactide from an optically pure lactic acid feed ispossible when utilizing appropriate conditions and catalysts. However,there is no teaching of a process which controls the optical purity ofthe resulting lactide to desired degrees or minimizes overall costs andmaximizes yield of the lactide product. Furthermore, there is nodisclosure of a commercially-viable lactide purification system, whichallows production of polymer grade lactide, from crude lactic acid,which may subsequently be polymerized to produce a variety ofnon-medical-related polylactide polymers suitable for replacing existingpetrochemical-based polymers.

Accordingly, a need exists for a continuous manufacturing process whichutilizes commercially-available lactic acid to produce polylactidepolymers suitable as a cost-competitive replacement forpetrochemical-based polymers. The present invention addresses this needas well as other problems associated with the production of lactidepolymers. The present invention also offers further advantages over theprior art, and solves other problems associated therewith.

SUMMARY OF THE INVENTION

The present invention provides a continuous process for the productionof lactide polymers from a crude lactic acid feed source. The crudelactic acid feed may be any available combination of the opticalenantiomers D-lactic acid and L-lactic acid in solution with ahydroxylic medium such as water or other solvent such as methanol,ethanol, propanol, butanol, isopropanol, isobutanol, or the like, ormixtures thereof. The source of lactic acid could also be an ester oflactic acid, such as methyl lactate, ethyl lactate, propyl lactate,butyl lactate, isopropyl lactate, isobutyl lactate or the like, ormixtures thereof. It is, however, recognized that the composition of thelactic acid feed source and the design and operating conditions of theprocess disclosed herein will affect the optical purity of the finalpolylactide polymer product. The process disclosed herein provides forthe control of racemization to advantageously produce a polymer gradelactide of selected optical purity and composition. Because racemizationcan be controlled, it is possible to project the optical purity andcomposition of the resulting product based on that of the startingmaterial. When polymerized, the resulting polylactide can have desirablephysical properties for a wide variety of non-medical relatedapplications. Furthermore, impurities such as color bodies,carbohydrates, proteins, amino acids, salts, metal ions, and othercarboxylic acids and organic acids may be present in the crude lacticacid feed. Applicants process disclosed herein overcomes problemsassociated with producing a polymer grade lactide when such contaminantsare present.

Referring now briefly to FIG. 1, which provides a preferred flowchart ofthe overall process disclosed herein, the crude lactic acid is first fedto an evaporator, continuously. Within the evaporator a portion of thewater or solvent or any condensation reaction by-product is removed fromthe crude lactic acid. The water or solvent or any condensation reactionby-product is removed as a vapor from the evaporator and discarded orrecycled. The evaporator thus concentrates the lactic acid in the crudefeed. It is believed there will be some condensation reaction occurringand the lactic acid may start to form oligomers and low molecular weightpolymers during the evaporation step, producing a condensation reactionby-product. This concentrated lactic acid is next fed to a prepolymerreactor, which in reality is a further evaporator.

It is well known in the art that as water or solvent are removed from asolution of lactic acid, the remaining lactic acid will begin topolymerize. In the prepolymer reactor, sufficient water or solvent andcondensation byproducts such as water, ethanol, methanol, propanol,butanol, isopropanol, isobutanol and the like are removed to cause thelactic acid to polymerize to form lactic acid polymers having an averagemolecular weight of about 100 to about 5000, preferably about 200 toabout 3000, and more preferably about 400 to about 2500. The water orsolvent removed is recycled or discarded. In preferred embodiments, thewater or solvent is recycled back to the evaporation process, because itmay be contaminated with lactic acid. In this preferred embodiment, lossof feed material is prevented and the overall yield is increased.

It is recognized by Applicants that the evaporation andprepolymerization stages may be combined into one step. However,Applicants have discovered the benefit of utilizing two steps that allowfirst removing uncontaminated water or solvent in the evaporation stepwhich is readily discarded or reused without treatment. The vapor streamfrom the prepolymerization reactor is greatly reduced in volume, yetcontains some lactic acid. Recycling back through the initialevaporation step allows recovery of any lactic acid carryover, thuspreventing loss of any valuable feed material.

The prepolymer product from the prepolymer reactor, polylactic acid orPLA, is fed to a lactide reactor. A catalyst is simultaneously andcontinuously fed to the lactide reactor. Many suitable catalysts areknown, such as metal oxides, metal halides, metal dusts and organicmetal compounds derived from carboxylic acids or the like. It isbelieved, any such catalyst may be utilized in the process disclosedherein. Polymer properties will, however, vary. In a preferredembodiment, the prepolymer and catalyst are mixed together in a staticmixer to facilitate an even distribution of catalyst within theprepolymer. The solution within the lactide reactor would quickly cometo an equilibrium distribution of lactide and polylactic acid with thetemperature and catalyst employed. Heat is added to vaporize the crudelactide which is continuously removed from the lactide reactor, thusdriving the depolymerization reaction, resulting in the net productionof lactide as the contents of the lactide reactor seek equilibrium. Itis believed that concentrations of unreactive high-boiling polylacticacid and other non-volatile impurities will concentrate in the solutionwithin the lactide reactor. It is believed this will require a purgestream to remove such impurities.

In a preferred embodiment of the present invention, a portion of thepurge stream of unreactive high boiling polylactic acid or othernon-volatile impurities in the solution within the lactide reactor maybe recycled to a point prior to the lactide reactor system or fed topolymerization. Based on experimental data which will followhereinbelow, it is believed that any long chain lactic acid polymerswill undergo transesterification to form lower molecular weightpolylactic acids which may be utilized as a feed source to the lactidereactor. This allows further maximization of yield due to reduced lossof valuable feed material.

The crude lactide vapor is composed of a mixture of all three possiblelactides: L-lactide, D-lactide, and meso-lactide, in variouscombinations. Along with the lactide, there is residual water, lacticacid and condensation reaction byproducts. This crude lactide may be feddirectly to a distillation system as a vapor for purification. In apreferred embodiment, this stream is fed to a partial condenser in whichthe lactide condenses and the majority of the water and other impuritiesremain as vapors and are recycled back to the lactide reactor or otherupstream process equipment such as the evaporator or prepolymer reactor.Preferably, the condensed crude lactide is fed directly to adistillation system for purification. Within this distillation systemresidual water and lactic acid are preferably removed as a distillateproduct and recycled back to the lactide reactor or other upstreamprocess equipment such as the evaporator or prepolymer reactor. Inaddition, provision may be made to remove low molecular weight oligomerswhich may be present in the crude lactide or formed during distillation.The purified lactide is preferably fed to a polymerization reactor ofconventional design.

The preferred overall process disclosed herein allows for the continuousmanufacture of lactide polymers from a crude lactic acid with little orno waste of raw material lactic acid feed. This is accomplished bymaintaining the crude lactide which was generated in the lactide reactoras a liquid or vapor and avoiding the yield loss associated with therecrystallization step traditionally used to purify the lactide. Thepurified lactide leaving the distillation system is further maintainedas a liquid and fed into a polymerization process. Other monomers may beadded to this purified liquid lactide prior to polymerization to achieveproduction of co-polymers of polylactide. Representative co-polymers aredisclosed by P. Dave, N. Ashar, R. Gross, S. McCarthy, "Survey ofPolymer Blends Containing Poly (3-hydroxybutyrate-co-16%hydroxyvalerate), Polymer Preparation, American Chemical Society, v. 31(1), pp. 442-3 (1990); B. Riedl and R. Prud'homme, "Thermodynamic Studyof Poly(vinyl chloride)-Polyester Blends by Inverse Gas PhaseChromatography", J. Polymer Science, Part B, vol. 24(11), pp. 2565-82(1986); H. Younes and D. Cohn, " Phase Separation in Poly(ethyleneglycol)/Poly(lactic acid) Blends, European Polymer J., v. 24(8), pp.765-73 (1988); Smith et al. (European Patent Application, EP 209371,Jan. 21, 1987); Pines et al. (European Patent Application EP 109197, May23, 1984); J. Zhu, Y. Shao, W. Sui, S. Zhang, H. Xiao and X. Tao,"Homopolymers and Copolymers of Glycolide and Lactide", C-MRS Int. Symp.Proc. Meeting Date 1990, v. 3, pp. 387-90 (1990); Jarrett et al. (U.S.Pat. No. 4,788,979); and, T. Nakamura et al., "Surgical Application ofBiodegradable Films Prepared from Lactide-Epsilon-CaprolactoneCopolymers, Advanced Biomaterials, 7 (Biomater. Clin. Appl.) pp. 759-64(1987).

Applicants believe any monomer capable of copolymerizing with lactidemay be used with the process disclosed herein.

In particular, this system allows recovery of any meso-lactide which maybe present or formed within the disclosed process and which is normallylost in a recrystallization process. Further, the problems associatedwith handling solid materials are eliminated. These problems arewell-documented by D. D. Deane and E. G. Hammond in "Coagulation of Milkfor Cheese-Making by Ester Hydrolysis", J. Dairy Science, v. 43, pp.1421-1429 (1960) and Nieuwenhuis et al. (U.S. Pat. No. 5,053,485) whichare incorporated herein by reference. The problems of storing suchsolids for any time period are also disclosed by Deprospero et al. (U.S.Pat. No. 3,597,449) and F. E. Kohn et al. in J. of Applied PolymerScience, Vol. 29, 4265-4277 (1984) which are incorporated herein byreference. These problems include contamination by water vapor whichwould lead to ring-opening side reactions causing the lactide to convertto lactic acid. The presence of lactic acid in the feed to the finalpolymerization step will result in polymers of limited molecular weight.

It is believed that the prior art does not teach use of distillation topurify crude lactide streams. Applicants believe that one would not turnto utilization of distillation due to the narrow differences betweenmelting point and boiling point of lactide streams, which potentiallycould cause solid plugging problems within a distillation system.Furthermore, side reactions in which the lactide ring is opened andpolymers of lactic acid are formed may occur during distillation. It isbelieved, the presence of such side reaction products would lead toundesirable molecular weight limitations in the final polymer product.Applicants have discovered that proper design and control of adistillation system coupled with direct feed of a crude lactide vaporstream or a liquid crude lactide stream after partial condensation toremove water and lactic acid vapor allows purification of crude lactidein a conventional distillation system. Previous to this disclosure,applicants believe, any polymer made from non-optically pure lactiderelied on blending the various lactide components, each of which hadbeen purified separately using recrystallization of a crude lactideproduced by other techniques.

The present system also allows use of crude lactic acid streams whichcontain impurities. As designed, the present system allows for removalof both low boiling and high boiling impurities prior to distillation ofthe crude lactide stream which is subsequently polymerized. The priorart fails to disclose a process with such advantages. Further,Applicants have found that impurities may prevent catalyst activation.In a preferred embodiment, this problem is overcome by first activatingthe catalyst by heating a mixture of the catalyst and purified lacticacid or lactide, then feeding such activated catalyst with the crudelactic acid feed. It is believed the prior art contains no suchteaching.

These and various other advantages and features of novelty whichcharacterize the present invention are pointed out with particularity inthe claims annexed hereto and forming a part hereof. However, for abetter understanding of the invention, its advantages, and the objectsattained by its use, reference should be made to the drawings which forma further part hereof, and to the accompanying descriptive matter, inwhich there are illustrated and described preferred embodiments of thepresent invention.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, in which like referenced numerals indicatecorresponding parts or elements of preferred embodiments of the presentinvention throughout the several views;

FIG. 1 is a flow diagram of the preferred overall process steps of thepresent invention;

FIG. 2 is a detailed schematic representation of a preferred polylactidepolymer production system in accordance with the present invention;

FIG. 3 is a graph showing the effects of sodium on lactide productionrate and optical purity;

FIG. 4 is a graph which represents the relationship between the opticalpurity of generated lactide in relation to the molecular weight of thefeed to the lactide reactor;

FIG. 5 is a graph showing the relationship between catalystconcentration and optical purity of the resulting lactide;

FIG. 6 is a graph showing the effect of hydroxyl impurities on polymermolecular weight at different temperatures;

FIG. 7 is a graph showing the effect of hydroxyl impurities on polymermolecular weight at different catalyst concentrations; and,

FIG. 8 is a graph showing the equilibrium lactide concentration as afunction of temperature.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As required, detailed embodiments of the present invention are disclosedherein. However, it is to be understood that the disclosed embodimentsare merely exemplary of the present invention which may be embodied invarious systems. Therefore, specific details disclosed herein are not tobe interpreted as limiting, but rather as a basis for the claims and asa representative basis for teaching one skilled in the art to variouslypractice the present invention.

Referring now to the figures, FIG. 2 represents an overall schematicflowchart encompassing the preferred process disclosed herein. A crudelactic acid feed (2) is provided. The crude lactic acid feed may be ofvarious grades. This could include USP, food grade, or any othersolution in a hydroxylic medium. A hydroxylic medium is a medium whichcontains molecules having a hydroxyl group, mediums such as water,methanol, ethanol, propanol, butanol, isopropanol, isobutanol and thelike, preferably having a number of carbon atoms in a range from 0-4,more preferably in a range from 0-2. The crude lactic acid can includefrom about 1% to about 99% by weight lactic acid, preferably, from about1% to about 85%, more preferably from about 5% to about 50%. In apreferred embodiment, the crude lactic acid feed is a solution of about15% lactic acid and about 85% water which is commercially produced. Manymanufacturing processes for producing crude lactic acid are known in theart, such as Glassner et al., (European Patent Application, EP 393818,Oct. 24, 1990); G. Machell, "Production and Applications of LacticAcid", Industrial Chemist and Chemical Manufacturer, v. 35, pp. 283-90(1959) and Kirk Othmer, Encyclopedia of Chemical Technology, "LacticAcid", v. 12, pp. 177-78 (2nd ed. 1963), which are incorporated hereinby reference. In an alternative embodiment, the source of crude lacticacid feed (2) could be in the form of the ester of lactic acid such asmethyl lactate, ethyl lactate, and the like. These esters are knownintermediate products of the lactic acid process disclosed above andincorporated herein by reference.

It is well known in the art that lactic acid includes two opticalisomers, the L and D enantiomers. Either optical isomer or anycombination thereof may be utilized as a crude lactic acid feed to thepresent reactor system. Furthermore, Applicants recognize that the crudelactic acid feed (2) may contain other impurities, such as color bodies,carbohydrates, proteins, amino acids, salts, metal ions, and othercarboxylic acids or organic acids. As will be explained in greaterdetail below, and in Example 1, the overall system incorporated in thepresent invention includes outlets for such impurities so that theirimpact on final polymer products is limited. These outlets aredesignated as (10), (28), (99), (71) and (66) of FIG. 2. Each will bediscussed in greater detail below. Thus, in preferred embodiments theneed for a more costly purified crude lactic acid feed is eliminated.

A fluid transfer mechanism (4) is provided to transport the crude lacticacid feed (2) through an optional static in-line mixer (6) in a pipeline(8) to an evaporator system (22). The evaporator system (22) is utilizedto concentrate the crude lactic acid feed (2) by removing water or anyother solvent or hydroxylic medium which is used as a carrier for thelactic acid, such as methanol, ethanol or the like and any condensationreaction by-products. The evaporator system (22) may be of anyconventional type known in the art, such as a multiple effectevaporator, a wiped film evaporator, a falling film evaporator, or anyother conventional system. It is appreciated that such systems may beoperated at pressures below atmospheric pressure, at atmosphericpressure or above atmospheric pressure with commensurate changes in heatload and operating temperatures. In a preferred embodiment, vacuumevaporation is utilized to reduce racemization. Water vapor or solventvapor, in reference to the hydroxylic medium or condensation reactionby-product, is removed from the evaporator via a transfer line (18), andcondensed in a condenser (16). The condensed liquid is transferred in apipeline (14) to a fluid transfer mechanism (12), such as a pump or thelike. The fluid transfer mechanism (12) transports the condensed wateror solvent via pipeline (10) as a waste stream and is discarded.

The lactic acid may be concentrated to a weight percent lactic acid ofabout 50% to about 99%, preferably from about 75% to about 99% and morepreferably from about 85% to about 99%. In a preferred embodiment, theevaporator system (22) is utilized to concentrate the crude lactic acidfeed from about 15% lactic acid up to about 85% lactic acid.

The concentrated lactic acid is transferred via a fluid transfermechanism (24) through a pipeline (26) to a prepolymer reactor (38). Theprepolymer reactor (38) is essentially a second evaporator system of anyconventional type which is utilized to further remove water or solventfrom the crude lactic acid feed. A portion of the water or solvent vapornow also includes such water or solvent produced from the lactic acidpolymerization reaction previously disclosed, the condensation reactionby-product. The water or solvent vapor leaves the prepolymer reactor(38) via line (32) and is condensed in a condenser (30). The condensedliquid is transferred via pipeline (36) to a transfer mechanism (34),with the transferred liquid comprising water or solvent with smallamounts of lactic acid and other impurities present. This liquid may bediscarded through line (28) or may be recycled through line (29) back toa static mixer or other mixing mechanism and fed once again through line(8) to the evaporator (22). The remaining liquid in the prepolymerreactor is continuously transferred via transfer mechanism (40) throughline (42) to a hold tank (44).

As previously disclosed, it is well recognized in the art that lacticacid undergoes a condensation reaction to form polylactic acid, thepolymer of lactic acid, as water is removed. In a preferred embodimentof the present system, the prepolymer reactor (38) is utilized to removeadequate water or solvent and condensation reaction by-product from thelactic acid to cause polymerization up to a molecular weight of about100 to about 5000, preferably about 200 to about 3000, and morepreferably about 400 to about 2500. As will be detailed in Example 2,which follows, in preferred embodiments the molecular weight of thepolylactic acid leaving the prepolymer reactor impacts the chemicalpurity as well as the optical purity of the crude lactide. This in turnwill affect the distillation and the properties of the final polymerproduct

Applicants recognize that the evaporator system (22) and the prepolymerreactor (38) could be combined into a single system which providedremoval of water or solvent sufficient to concentrate the lactic acidfeed and also to polymerize such lactic acid. In the preferredembodiment, as discussed above, the systems are separate to takeadvantage of recognized differences in the composition of the vaporleaving the evaporator (22) at line (18) and the vapor leaving theprepolymer reactor (38) in line (32). The first step of concentratingthe crude lactic acid in the evaporator (22) from 15% lactic acid to 85%lactic acid results in substantially pure water or solvent leaving theevaporator in line (18), which may be readily discarded withouttreatment. The vapor in line (32) leaving the prepolymer reactor (38)will necessarily contain lactic acid and other impurities which arecarried over in the evaporation process. These impurities willpreferably need to be recycled or treated before discarded. Thus, in thepreferred embodiment, Applicants take advantage of the economic benefitsof removing nearly pure water (or solvent) in the evaporator (22) andreduced recycle or waste treatment of the vapor leaving the prepolymerreactor (38).

Applicants also recognize that the evaporator system (22) and prepolymerreactor (38) may be replaced by a series of batch evaporators thatconcentrate the lactic acid and produce prepolymer. The series of batchsystems may be operated to provide a net continuous supply ofprepolymer.

The hold tank (44) is maintained at a temperature sufficient to keep thepolylactic acid in a flowable liquid state. The hold tank (44) is,however, only a feature of the preferred embodiment, recognizing thecontrol problems which may result from direct feed to the lactidereactor (60). This liquid is transferred via transfer mechanism (46)through a pipeline (48) to a static in-line mixer or other mixingmechanism (50). Within the mixing mechanism (50) a catalyst is added tothe polylactic acid. Applicants recognize that any means of adding thecatalyst to the polylactic acid would be appropriate; however, thestatic mixer (50) utilized in the preferred embodiment allows more evendistribution of the catalyst within the liquid. The catalyzed polylacticacid is transferred via transfer line (54) to the lactide reactor (60).It is well recognized in the art that polylactic acid maintains adynamic equilibrium with its depolymerization product, lactide, asrepresented by the reaction below: ##STR4##

It is further recognized that this reaction is catalyzed by suchcompounds as tin dust, tin halide, tin oxide, and organic tin compoundsderived from C₁ -C₂₀ carboxylic acids, as disclosed by Muller in U.S.Pat. No. 5,053,522, which is incorporated herein by reference. Othermetals, such as zinc, and their halides, oxides and organic compoundsthereof, have been recognized by the art as possible catalysts for thelactide reaction. It is believed any metals of Groups IV, V or VIII ofthe Periodic Table and compounds thereof, are possible catalysts forgenerating lactide. In a preferred embodiment tin oxide is utilized ascatalyst. In a most preferred embodiment the catalyst is activated priorto feed.

As lactide is generated within the lactide reactor (60), it is removedas a vapor continuously through line (58). The removal of lactidefurther drives the depolymerization reaction. It is believed that somehigh-boiling or non-volatile contaminants present in the feed to theentire system will concentrate in the lactide reactor and necessitateinclusion of a purge stream (62). Example 1 below details the effect ofcationic impurities and Example 11, the detrimental effects ofconcentrating metal ions in the lactide reactor (60). It is believedother impurities would have a similar effect and necessitate the purgestream (62). A portion of this purge stream (56) may be recycled back tothe static mixer (50) and recatalyzed and fed to the lactide reactor(60). Alternatively, the purge stream may be fed to the polymerizationreactor (110) via line (68), if such polymer is desired. A transfermechanism (64) is provided to transport the purge stream optionally to apoint prior to the evaporator (22) such as the static mixer (6) or tothe feed line (26) to the prepolymer reactor (38) or to waste throughline (66) or to a static mixer (104) for polymerization in apolymerization reactor (110).

The lactide vapor leaving the lactide reactor (60) in line (58) ispartially condensed in a condenser (72). The uncondensed vapor consistsof residual lactic acid and water or solvent, along with some lactidewhich remains uncondensed. This vapor stream leaves the system throughline (90) and is condensed in a condenser (92), the liquid thus beingtransferred by transfer mechanism (96) through line (94). This liquidmay optionally be discarded through line (99) or recycled through line(98) back to the crude lactic acid static mixer (6). In the preferredembodiment, this stream is recycled in order to recover and utilize anylactic acid or lactide which is not condensed in partial condenser (72).

The condensed crude lactide leaving condenser (72) via line (74) istransferred via fluid transfer mechanism (76) through line (78) to adistillation system (80) for purification of the lactide. Applicantsrecognize that partial condensation may not be necessary and the crudelactide vapor may be fed directly to the distillation system (80). Thedistillate leaving the distillation system (80) in line (82) is composedof water or solvent, some residual lactic acid, and some lactidecarryover. This stream is condensed in condenser (84) and transferredvia fluid transfer mechanism (88), in line (86), and may be discarded orrecycled back to a point prior to the evaporator (22), such as thestatic mixer (6) or the feed line (26) to the prepolymer reactor (38)through line (71), or more preferably recycled in line (70) back to thestatic mixer (50) to be recatalyzed and re-fed to the lactide reactor(60). This preferred embodiment allows minimization of waste bypreventing loss of lactic acid or converting lactic acid to lactide fromthe feedstock.

The refined lactide is removed from the distillation system (80) viatransfer mechanism (100) in line (102) and fed to a polymerizationreactor (110). Applicants recognize that the distillation system (80)may include more than one distillation column or a flash drum. Thepolymerization process may be of any conventional design known to theart, such as that disclosed by J. Leenslag and A. Pennings, "Synthesisof High Molecular Weight Poly (L-lactide) Initiated with Tin2-Ethylhexanoate", Makromol. Chem., v. 188, pp. 1809-14 (1987) and F.Kohn et al., "The Ring-Opening Polymerization of D,L-Lactide in the MeltInitiated with Tetraphenyltin, J. Applied Polymer Science, v. 29, pp.4265-77 (1984), which are incorporated herein by reference.

Applicants recognize that in a preferred embodiment one may choose toadd a non-lactide monomer to the purified lactide leaving thedistillation system (80). This co-monomer may be added via line (101).The co-monomers are fed to the polymerization reactor (110) andpolymerized to form a co-polymer. Many co-polymers of polylactide areknown to the art. These include P. Dave, N. Ashar, R. Gross, S.McCarthy, "Survey of Polymer Blends Containing Poly(3-hydroxybutyrate-co-16% hydroxyvalerate), Polymer Preparation,American Chemical Society, v. 31 (1), pp. 442-3 (1990); B. Riedl and R.Prud'homme, "Thermodynamic Study of Poly(vinyl chloride)-PolyesterBlends by Inverse Gas Phase Chromatography", J. Polymer Science, Part B,vol. 24(11), pp. 2565-82 (1986); H. Younes and D. Cohn, "PhaseSeparation in Poly(ethylene glycol)/Poly(lactic acid) Blends, EuropeanPolymer J., v. 24(8), pp. 765-73 (1988); Smith et al. (European PatentApplication, EP 209371, Jan. 21, 1987); Pines et al. (European PatentApplication EP 109197, May 23, 1984); J. Zhu, Y. Shao, W. Sui, S. Zhang,H. Xiao and X. Tao, "Homopolymers and Copolymers of Glycolide andLactide", C-MRS Int. Symp. Proc. Meeting Date 1990, v. 3, pp. 387-90(1990); Jarrett et al. (U.S. Pat. No. 4,788,979); and, T. Nakamura etal., "Surgical Application of Biodegradable Films Prepared fromLactide-Epsilon-Caprolactone Copolymers, Advanced Biomaterials, 7(Biomater. Clin. Appl.) pp. 759-64 (1987), which disclosures areincorporated herein by reference. Applicants believe any co-polymers ofpolylactide may be produced from the process disclosed herein.

Fluid transfer mechanisms disclosed throughout this detailed descriptionwould normally be a pump. However, Applicants recognize that throughdesign choices other mechanisms for transfer, such as gravitationalflow, may also be utilized.

Applicants further recognize that the preferred overall system describedherein is a complex combination of many known chemical engineering unitoperations. So that the benefit of the overall combination may berecognized, Applicants herein disclose in further detail the selection,operation, and benefits of selecting such unit operations, along withactual laboratory experimental results exemplifying the disclosedadvantages.

As previously stated, the crude lactic acids fed to this process (2) maybe made up of L-lactic acid or D-lactic acid, or combinations thereof.The composition of the feed, however, does not translate directlythrough the entire process to define the composition of the polymerproduct leaving the polymerization reactor (110) through line (108).Applicants recognize that racemization, or conversion of one opticalenantiomer to the other, may occur. It is believed that suchracemization is driven by such factors as temperature, pressure, time ata given temperature or pressure, the presence of catalysts orimpurities, and relative concentrations of the two enantiomers at anygiven time. The degree of racemization is defined herein by the percentconversion of the optical enantiomer that is present in excess of 50%.As an equation, this calculation would be defined as: ##EQU1## Thus, aninitial composition of 75% L and 25% D, which results after racemizationto a 50% L, 50% D mixture, would equate to a degree of racemization of100%. In all instances, no matter what initial composition, a 100%degree of racemization coincides with a composition of 50% eachenantiomer, or optical inactivity. This recognizes the tendency towardequilibrium at a 50% of concentration of each enantiomer, correspondingto optical inactivity. In the most preferred embodiment of the system,each unit operation is controlled to a degree that allows production ofa purified lactide mixture with selected chemical and opticalcomposition. The optical composition of the lactide mixture isdetermined by the relative abundance of D- and L-lactic acid sub-unitsin the polylactic acid within the lactide reactor. As recognized byNieuwenhuis et al. in U.S. Pat. No. 5,053,485, the disclosure of whichis incorporated herein by reference, the blend of lactide isomers usedto produce the polymer affects the physical properties of the polymer,including the biodegradability.

In a preferred embodiment, the evaporator (22) is operated to minimizeresidence time so that there is little or no effect on optical purity.The prepolymer reactor (38) is also operated to minimize racemization.This includes reducing the residence time within the reactor.

The crude lactide produced in the lactide reactor (60) will be a mixtureof the three possible lactides which may be generated from L- andD-lactic acid. These include an L-lactide, a D-lactide, andmeso-lactide.

As detailed in Example 3 hereinbelow, the concentration of catalystadded to static mixer (50) also affects the degree of racemization andcomposition of the crude lactide product. In a preferred embodiment, thecatalyst concentration level is adjusted based on desired properties ofthe final polymer product.

Applicants have discovered, and detailed in Example 12, that the qualityof the crude lactide charged to the distillation system has asignificant effect on the operation of said system. In particular,acidic impurities such as lactic acid and low molecular weightoligomers, which are formed by ring opening reactions of lactic acid orwater with lactide, can cause premature polymerization in thedistillation system. In a preferred embodiment, applicants believe suchside reactions may be controlled by partially condensing the crude vaporprior to feeding to distillation to remove impurities.

The distillation system (80) may also be operated to controlracemization of the lactide and other side reactions. In a preferredembodiment, this system is designed to minimize racemization byutilizing a packed column distillation system which minimizes liquidholdup, along with a thermal-siphon reboiler which limits residence timeof the bottom liquids, and utilizing a minimum reflux ratio to furtherreduce holdup time in the column. It is, however, recognized that otherdistillation systems may be utilized with varying impact on the opticalpurity of the purified lactide and resultant polymer product.

In a preferred embodiment, the distillation system (80) is utilized as apurification step for the lactide so that crystallization of the crudelactide is unnecessary in order to produce a lactide product of suitablepurity for polymerization. The lactide reactor (60) is also designed ina preferred embodiment, maximizing surface area between liquid and vaporso that liquid lactide can more easily vaporize. This allows for rapidremoval of the generated lactide, which in turn further drives thereaction. Furthermore, as recognized by DeVries in U.S. Pat. No.4,797,468, which is incorporated herein by reference, a system whichutilizes purification steps other than crystallization increases yield.The use of distillation as a purification step also prevents the need tohandle solids with the problems with equipment and contaminationinherent in such operations.

The following examples further detail advantages of the system disclosedherein:

EXAMPLE 1 Effect of Cationic Impurities on Optical Purity

Na₂ S was added at levels of 20, 200, and 1000 ppm to purified lacticacid (Purac heat stable grade) of composition 85% L-lactic acid and 15%water. The lactic acid was then polymerized to form PLA with a numberaverage molecular weight of about 650 g/mol. H₂ S was removed undervacuum while the PLA was being formed, leaving Na⁺ ions in solution. ThePLA was then used to generate lactide at 10 mm Hg with 0.05 wt-% SnOcatalyst (Aldrich cat. no. 24,464-3, Tin (II) oxide, 99+%) and aconstant heat input of 75%, allowing reactor temperature to float. Theresults are shown in the following table and in FIG. 3:

    ______________________________________                                        EFFECT OF SODIUM ON LACTIDE PRODUCTION                                        RATE AND OPTICAL PURITY                                                       Sodium   Production                                                           sulfide, rate,          Meso,   Temp                                          ppm      hr.sup.-1      wt %    (°C.)                                  ______________________________________                                          0      0.73            5.3    234                                            20      0.74            7.5    235                                            200     0.60           23.4    238                                           1000     0.76           36.6    233                                           ______________________________________                                    

The table shows that although the addition of sodium had no effect onthe lactide production rate or on the reaction temperature, it did havea pronounced effect on the amount of meso-lactide present in the crudeproduct.

Applicants believe other cationic species will behave in a similarfashion.

A practical implication of this example is that it will be necessary inany continuous process, where management of optical composition isdesired, to provide a mechanism for removing ionic impurities from thereactor. The ionic impurities will be present in all sources of lacticacid to some extent, and will concentrate in the liquid within thelactide reactor (reactor bottoms) over time. In a preferred embodimentof the present invention, a purge stream is provided to accomplish thisobjective. An alternative would be to shut the system down periodicallyand dump or recycle the reactor bottoms.

EXAMPLE 2 The Effect of PLA Molecular Weight on Optical Purity

Lactide was generated from several samples of PLA (also known aspolylactic acid or prepolymer) each sample having a different averagemolecular weight. The conditions under which the lactide was generatedin each experiment include: 10 mm Hg pressure, 0.05 wt-% SnO as catalyst(same catalyst as Example 1), run to approximately 73% conversion of PLAto lactide, constant heat input and stirring speed. The reactiontemperature was allowed to float, reaching the value necessary todissipate the heat input. This method of running tends to give aconstant lactide production rate, within limits. Five samples of PLAwere used, a reference case with molecular weight of 640 g/mol(determined by end group titration) and four additional cases obtainedby further heating of the PLA under vacuum at 200°-220° C. The resultsof the experiments are tabulated below and shown in FIG. 4.

    ______________________________________                                        Feed                                                                          Avg.    Add.   PLA      Reac. Lactide                                         Molecular                                                                             Heat   Temp     Temp  Rate         % Lac-                             Weight  (hr.)  (C.°)                                                                           (C.°)                                                                        (hr..sup.-1)                                                                        % Meso tic acid                           ______________________________________                                         640    0        200    234   0.73   5.3   5.3                                1140    1      200-210  225   0.89   6.8   2.9                                1350    1.5    210-220  233   0.76   8.1   2.5                                1800    3.8    200-215  252   0.76  10.1   2.3                                3100    6.5    200-210  257   0.78  11.2   1.7                                ______________________________________                                    

Increasing the feed molecular weight results in a very clear decrease inthe concentration of lactic acid in the crude lactide. This is aprocessing benefit because it will be easier to achieve polymerizationgrade lactide from a cleaner starting material. However, as the tableand figure show, the concentration of meso-lactide in the crude lactideincrease significantly. The optimal operation will require carefulbalancing of these two factors based on the desired final polymerproduct. In particular, if lactide of high optical purity is desiredthen the process should be run with a low molecular weight feed.

EXAMPLE 3 The Effect of Catalyst Concentration on Optical Purity

Lactide was produced using SnO catalyst (catalyst of Example 1) from PLAwith a molecular weight of 650 g/mol at several catalyst levels and twopressures. The power input was held constant (Varian setting of 75) andthe reaction temperature was allowed to seek an equilibrium level. Thepercentage meso in the crude lactide for each experiment is shown in thetable below and graphically in FIG. 5.

    ______________________________________                                                   Catalyst                                                           PRESSURE   conc.         Meso.   Temp                                         (mm Hg)    wt %          wt %    (C.)                                         ______________________________________                                         1         0.010         3.5     245                                           1         0.025         3.4     230                                           1         0.030         2.6     213                                           1         0.500         3.8     200                                          10         0.010         4.1     231                                          10         0.025         3.8     220                                          10         0.050         4.0     210                                          10         0.100         4.3     210                                          10         0.500         5.1     197                                          10         1.000         6.3     195                                          ______________________________________                                    

It is clear from this data that Catalyst levels above 0.1 wt-% lead toan increase in the content of meso-lactide, for both pressures studied.The increase occurs even though the overall lactide generation rateincreases and the reaction temperature decreases. The content ofmeso-lactide also increases at very low concentrations of catalyst,resulting in a minimum for 0.02-0.10 wt-% SnO. In a preferredembodiment, catalyst concentrations may be varied depending on desiredfinal polymer physical properties.

EXAMPLE 4 The Effect of Recycling Lactide Reactor Bottoms

Example 1 demonstrated that some form of purge of the liquid in thereactor (reactor bottoms) would probably be necessary for a continuousoperation. This example demonstrates a surprising benefit if such purgestream is recycled back to the catalyst addition stage.

PLA was produced from the same lactic acid used in Example 1, utilizingthe same method. This was used to generate lactide at 1 mm Hg with 0.05wt-% SnO as catalyst (catalyst of Example 1). The reaction was run to72% conversion, at which point the lactide production rate had begun todecline significantly. The heat was turned off and the flask was cooledto 150° C. under a nitrogen atmosphere. 390 gms of 88% L-lactic acid wasadded to the 80 gms of residue. The flask was adapted to generate a newbatch of PLA, simulating the recycle of reactor bottoms to theevaporator section. The new PLA was heated under vacuum until themolecular weight was about 650 g/mol (by end group titration). A GPC(gel permeation chromatography) analysis showed that the reactor bottomshad been completely broken down and been reabsorbed into the PLA, withno sign of high molecular weight reactor bottoms. The lactide generationwas rerun using the same conditions as before, and it was surprisinglyfound that the lactide production rate increased: from 0.86 hr⁻¹ for thefirst run (prior to recycle) to 1.03 hr⁻¹ for the second run (recycle,no additional catalyst). The reaction temperature was 213° C. for thefirst run and 215° C. for the second run. The composition of the crudelactide and of the reactor bottoms were similar for the two cases. Thus,in a preferred embodiment the reactor bottoms is recycled to a pointprior to the lactide reactor to increase overall yield from the lacticacid feed.

EXAMPLE 5 Polymerization Technique

The lactide is a mixture of 80% L- and 20% D,L-lactide, recrystallizedto high purity. 40 gm of lactide is charged to a flask with magneticstirring. A THF (Tetrahydrofuran, Burdick and Jackson, high purity,non-spectro) solution containing L-lactic acid, water, or both is addedto the lactide. The flask is lowered into an oil bath at 140°-160° C. tomelt and mix the monomer. This is held for five minutes after completemelting (about 15 minutes total). A starting sample is pulled for GCand/or water analysis. A catalyst solution of 10 wt. % Tin(II)2-Ethylhexanoate (Johnson Mathey Electronics, Tech. Grade) in toluene isadded and allowed to react for 1 minute. Five gram samples are thenpipetted into silanized and nitrogen flushed 20 ml vials. These arequickly placed into a temperature controlled oil bath. Vials are pulledand frozen at various time intervals up to 4 hours.

The samples are prepared for analysis by breaking the polymer out of thevials and dissolving in THF at room temperature on an orbital shaker(about 1-6 hours for 5 grams of polymer in 125 mls THF). The mixture isthen diluted to 1% in THF and analyzed utilizing GPC analysis todetermine the molecular weight and percent conversion.

EXAMPLE 6 Polymer Molecular Weight is Controlled by Impurity Level andis Independent of Temperature

Experiments were conducted at three different temperatures with twolevels of impurities, using the polymerization technique of Example 5.In each case, a projected molecular weight which the polymer wouldachieve at 100% conversion was determined by GPC analysis of the highestconversion sample and corrected for the unconverted monomer. This methodhas been shown to give reproducible values and accurately corrects forany effect of sampling at different conversion levels. The results ofthe experiments are tabulated below and shown graphically in FIG. 6.

    ______________________________________                                                    Hydroxyl                                                          Temperature impurities                                                                              Molecular weight,                                       (°C.)                                                                              meq/mol   adjusted to 100% conv.                                  ______________________________________                                        173         4.45      40,100                                                  173         2.52      77,500                                                  186         3.90      37,800                                                  186         2.38      72,100                                                  199         3.98      39,400                                                  199         2.48      74,900                                                  ______________________________________                                    

A statistical analysis of variance showed that the molecular weight ofthe polymer was controlled solely by the level of impurities, withtemperature having no effect. Thus, in a preferred embodiment hydroxylimpurities are controlled to desired levels to control the physicalproperties of the resulting polymer product.

EXAMPLE 7 Polymer Molecular Weight is Controlled by Impurity Level andis Nearly Independent of Catalyst Concentration

The polymers were prepared at 160° C. using the polymerization techniqueof Example 5. Two levels of water (H=5.9-8.8 meq./mol., L=1.8-3.7meq./mol.) and two levels of lactic acid (H=0.9-1.3 meq./mol., L=0.1-0.2meq../mol.) were used in a duplicated factorial design experiment ateach of two different levels of catalyst (0.0002 mol/mol; and 0.0004mol/mol) (eight experiments total). Projected molecular weights werecalculated as in Example 6. The results are shown in tabular form belowand graphically in FIG. 7.

    ______________________________________                                                          Total     Molecular                                                           Hydroxyl  weight adjusted                                   Water Impurity level                                                                            Content   to 100%   Catalyst                                conc. Lactic acid meq/mol   conversion                                                                              Level                                   ______________________________________                                        L     L           4.49      133,500   0.002                                   H     H           11.35     33,900    0.002                                   L     H           5.36      74,500    0.002                                   H     L           9.20      29,400    0.002                                   L     H           4.65      89,800    0.004                                   H     H           8.31      34,900    0.004                                   L     L           2.52      160,600   0.004                                   H     L           8.89      32,700    0.004                                   ______________________________________                                    

An analysis of variance revealed that the change in hydroxyl contentaccounted for 91% of the variance in the molecular weight, while thechange in catalyst concentration accounted for only 4% of the variance.Both effects were found to be statistically significant.

These data show, in a preferred embodiment, the critical need to controlthe level of hydroxyl containing impurities in the lactide in order tocontrol the molecular weight of the final polymer.

EXAMPLE 8 Equilibrium Concentration of Lactide in Polylactic-Acid

PLA of 650 MW was heated at atmospheric pressure with either 0.00, 0.05,or 0.15 wt % SnO as a catalyst (Catalyst of Example 1). The mixtureswere held at three different desired temperature for 20 minutes, atwhich time 10 wt % of purified L-lactide was added to the mixture withstirring. The vessel was fitted with a condenser to prevent the loss ofwater or other volatile components. Samples were removed from thereaction vessel at times ranging from 5 minutes to 450 minutes and wereanalyzed using an Ultrastyragel®100A GPC column (Waters Chromatography,a division of Millipore Corp.) with THF as the mobile phase to determinethe concentration of lactide. The concentration data were fit to asimple first order decay model using a non-linear regression softwarepackage (SAS Institute, Inc.) to determine the equilibrium values. Theresulting projected values for the equilibrium concentrations of lactideare shown in the table below and plotted graphically in FIG. 8. Theresults show the beneficial effect of rapid removal of lactide from thelactide reactor in preferred embodiments to further drive the lactidegeneration reaction.

    ______________________________________                                        Temperature  Catalyst   Equilibrium lactide,                                  (°C.) conc., wt %                                                                              wt %                                                  ______________________________________                                        140          0.05       3.50                                                  140          0.15       3.30                                                  170          0.05       4.00                                                  170          0.05       3.57                                                  170          0.15       4.13                                                  170          0.15       3.85                                                  200          0.00       5.12                                                  200          0.05       5.38                                                  200          0.05       4.82                                                  200          0.15       5.47                                                  200          0.15       5.20                                                  ______________________________________                                    

EXAMPLE 9 Relative Rates of Racemization

Samples of PLA (with and without SnO (Catalyst of Example 1) ascatalyst) and lactide were heated and stirred for four hours at 200° C.at atmospheric pressure in a round bottom flask fitted with a condenserto prevent loss of volatile components. The samples were then allowed tocool and the optical purity of the PLA was determined by saponificationfollowed by a measurement of the optical rotation. The lactide samplewas analyzed by GC to determine the meso-lactide content, which was thenconverted to a measurement of optical purity.

    ______________________________________                                                          Optical                                                                       Composition                                                 Sample              % L    % D                                                ______________________________________                                        Initial PLA         96.0   4.0                                                PLA, no catalyst    95.4   4.6                                                PLA, 0.05 wt % SnO  87.5   12.5                                               PLA, 0.15 wt % SnO  90.0   10.0                                               Initial lactide     99.7   0.3                                                Lactide after heating                                                                             97.2   2.8                                                ______________________________________                                    

The results of this experiment demonstrate that racemization occursfastest in PLA which is exposed to catalyst. Thus, in the most preferredembodiment racemization is controlled in the lactide generating reactor.It is however recognized that another area of racemization control willbe the evaporators which are used to prepare PLA, because of the longresidence times and the possible inclusion of catalyst and catalyzingimpurities. In a preferred embodiment the residence time of the lactidein the distillation column will be kept low, minimizing the potentialfor racemization.

EXAMPLE 10 Effect of Mass Transfer Efficiency on Lactide Composition

Lactide was produced from PLA at several catalyst levels and at twopressures to determine the effect of mass transfer. The catalyst was SnO(Catalyst of Example 1) and the power setting of the Varian was 75%.

The table below shows the effect of changing mass transfer efficiency byadjusting the pressure (vapor phase lactide concentration). Note thatthe reaction temperatures were similar for each pair of cases.

    ______________________________________                                        Catalyst                                                                             1 mm Hg          10 mm Hg                                              conc., wt      meso,   net rate     meso, net rate                            % SnO  T (°C.)                                                                        wt %    (hr.sup.-1)                                                                          T (°C.)                                                                      wt %  (hr.sup.-1)                         ______________________________________                                        0.05   213     2.6     0.79   210   4.0   0.46                                0.50   200     3.8     0.83   197   5.1   0.52                                ______________________________________                                    

The increased mass transfer efficiency at 1 mm Hg vs 10 mm Hg results insignificantly higher net lactide production rates and a lowerconcentration of meso-lactide. In a preferred embodiment the lactidereactor is operated under vacuum to facilitate mass transfer.

EXAMPLE 11 The Effects of Metal Contaminants Concentrating In theLactide Reactor

Lactic acid was concentrated and polymerized to form low molecularweight polylactic acid (MW range of about 600-2200) and fed to acontinuous pilot scale reactor for the production of lactide. At the endof 1-week of operation a sample of the reactor liquid was taken andanalyzed for metals. The results are shown below.

    ______________________________________                                               Iron          1200 ppm                                                        Chromium       310 ppm                                                        Nickel         180 ppm                                                        Sodium         89 ppm                                                         Calcium        55 ppm                                                         Manganese      26 ppm                                                         Magnesium      13 ppm                                                         Copper          6 ppm                                                         Potassium     ND                                                       ______________________________________                                    

The metals profile clearly shows corrosion of the stainless steelreaction system, either in the formation of the prepolymer or in thelactide generating reactor.

The high metals content, which represents the build-up over a week withno purge on the reactor bottoms, is detrimental to the lactide formationprocess. The data below demonstrate this effect.

Three lactide runs were made following the usual laboratory process. Acontrol using 650 MW PLA, the control with added iron and chromium (1000ppm iron from FeCl₃ *6H₂ O, 1000 ppm iron from FeSO₄ *7H₂ O, and 1000ppm chromium from CrCl₃ *6H₂ O), and the reactor bottoms sample (initialMW 2000). Fresh catalyst, 0.05 wt % SnO (Catalyst of Example 1), wasadded to each sample and lactide was generated at 10 mm Hg with areactor temperature of 230-240° C.

    ______________________________________                                                               Rate                                                   Sample         Yield   (hr.sup.-1)                                                                            MW.sub.n                                                                            MW.sub.w                                ______________________________________                                        Control PLA    73%     0.73     3100   13300                                  Control PLA + metals                                                                         63%     0.90     9900  126400                                  Reactor sample 42%     0.42     6400  143400                                  ______________________________________                                    

The runs with elevated metals content had lower yield and much higherweight average molecular weight at the end of the reaction,demonstrating the detrimental effects of a high metal content.

It is believed that in a preferred embodiment, a purge of the reactorbottoms will alleviate this problem.

EXAMPLE 12 The Effect of Acidic Impurities on Distillation

Lactide was produced in a continuous pilot plant at rates of 2-5 kg/hr.The starting materials were Purac lactic acid of about 85%concentration. A PLA prepolymer having a range of molecular weights fromabout 400-2000 MW was made batchwise by heating first at atmosphericpressure and then under vacuum. The prepolymer was used to supply thecontinuous feed to the lactide reactor. The reactor was run at atemperature of 220°-240° C. and pressure of about 35 mm Hg.

Two samples of lactide were distilled in a 2000 ml three-neck flask withmechanical stirring. The lactide was taken overhead through a 2 cm ID by30 cm glass column with stainless steel packing. Reflux was notcontrolled, but the column was insulated. The rate of distillationranged from about 150-370 gms/hr. After taking approximately 80%overhead, the bottoms were analyzed by GC to determine the concentrationof oligomers and to calculate the amount of polymerization (based onfeed) which had occurred. The table below shows the relationship betweenthe concentration of acidic impurities in the crude lactide and theextent of polymerization during distillation. The data show the effectof acidic impurities on final polymer molecular due to the increasedoligomer content in the purified lactide.

    ______________________________________                                              Acidic Impurity                                                               meq [COOH]/ Percent of Charge                                                                          Oligomer Increase                              Sample                                                                              mol lactide taken overhead                                                                             as % of feed                                   ______________________________________                                        #1    19          92%          0.5%                                           #2    43          80%          7.6%                                           ______________________________________                                    

EXAMPLE 13 The Beneficial Effects of Catalyst Activation on LactideGeneration Rates

Three grades of PLA were evaluated for the production of lactide usingvarious catalysts. The sources of the PLA were: A) Purac heat stablegrade lactic acid, B) a test sample of lactic acid from Lactech, Inc.which was produced by fermentation, and A/B) a 50/50 mix of the PLAproduced from each of the previous two sources.

Lactide was generated in a laboratory apparatus (three-neck flask withmechanical stirring, primary condenser operated at 85°-100° C., andreceived flasks and traps) at constant temperature of 230° C. andconstant pressure of 10 mm Hg. Initial PLA charge was 360 gms ofmaterial having an average molecular weight of about 650. The catalystcharge was 0.045 wt % as Sn for each type of catalyst.

Table 1 shows the results of several experiments for differentcombinations.

    ______________________________________                                                           Crude lactide                                                                            Overall rate                                    PLA    Catalyst    yield, wt %                                                                              (gm/gm hr PLA)                                  ______________________________________                                        A      none        42         0.20                                            A      SnO         68         0.70                                            A/B    SnO         50         0.30                                            A      SnCl.sub.2  78         1.90                                            B      SnCl.sub.2  76         1.30                                            A      Sn Octonoate                                                                              74         1.90                                            B      Sn Octonoate                                                                              75         1.50                                            ______________________________________                                    

From the table above it can be readily seen that PLA B is not asreactive toward lactide production as is PLA A. The effect isparticularly pronounced with SnO catalyst.

Analysis of the initial lactic acids did not reveal any significantimpurities in B relative to A. It is believed that some unidentifiedcontaminant in PLA B blocks catalyst activity.

Further experiments were performed using the liquid contents of thelactide reactor (reactor bottoms or bottoms) from previous runs with SnOcatalyst as the catalyst. The overall Sn content was maintained at 0.045wt %.

    ______________________________________                                                Catalyst/ Crude lactide                                                                              Overall rate                                   PLA     Bottoms   yield, wt %  (gm/gm hr PLA)                                 ______________________________________                                        A       SnO/(A/B) 46           0.31                                           A       SnO/A     65           1.20                                           B       SnO/A     71           1.17                                           B       SnO/A     70           1.22 (replicate)                               ______________________________________                                    

The table above clearly shows that lactide can be produced from PLA B asfast as from PLA A if the SnO catalyst is pretreated by first producinga batch of lactide from PLA A. The table also shows that if the catalystis pretreated by producing a batch of lactide from the blend A/B PLAthen it is rendered ineffective and does not promote lactide productionat high rates even from PLA A. Thus, applicants have surprisingly foundthat apparent deficiencies in the lactic acid source can be overcome byproper conditioning of the catalyst.

Comparison of the rates for PLA A with SnO (0.70 hr⁻¹ table 1) and SnO/A(1.20 hr table 2) shows that the conditioning also increases the overallrate of the reaction for the most productive lactic acid, providing anadditional benefit.

Applicants believe that heating the catalyst at about 200°-230° C. forabout 10-30 minutes in the presence of either 1) PLA made from apurified lactic acid, 2) PLA prepared by the partial hydrolysis ofpurified lactide, 3) purified lactic acid, or 4) lactide, would providesimilar benefits as the method described above.

EXAMPLE 14 Distillation of Crude Lactide

The overhead fraction from example 12 was collected in three receivers,containing 14%, 36%, and 28% of the crude lactide charge, respectively.The first fraction contained over 5 wt % lactic acid and was discarded.Fractions 2 and 3 were combined and redistilled, yielding a lactidefraction with total acidic impurities of 4.4 milliequivalents/mol oflactide. This fraction was polymerized using the polymerizationtechnique of example 5 (temperature 180° C., catalyst/monomer ratio1:5000), yielding a polymer with number average molecular weight of42,100 at 100% conversion and weight average molecular weight of 76,300.Actual conversion was 84.6% at 2 hours.

Applicants believe this final example, coupled with previous examplesdemonstrates the overall feasibility and advantages of the disclosedprocess.

It will be understood, however, that even though these numerouscharacteristics and advantages of the invention have been set forth inthe foregoing description, together with details of the structure andfunction of the invention, the disclosure is illustrative only, andchanges may be made in detail, especially in matters of shape, size andarrangement of the parts or in the sequence or the timing of the steps,within the broad principle of the present invention to the full extentindicated by the broad general meaning of the terms in which theappended claims are expressed.

What is claimed is:
 1. A process for the continuous conversion of acrude lactic acid feed in an aqueous medium to substantially purifiedlactide, said process comprising the steps of:a) providing a source oflactic acid in an aqueous medium; b) concentrating the lactic acid inthe aqueous medium by evaporating a substantial portion of the aqueousmedium to form a concentrated lactic acid solution; c) polymerizinglactic acid in the concentrated lactic acid solution of step (b) byfurther evaporation of the aqueous medium to form polylactic acidmolecules having an average molecular weight of between about 100 andabout 5000; d) forming a crude lactide in the presence of catalyst meansfor catalyzing the depolymerization of the polylactic acid molecules toform lactide molecules, and e) purifying the crude lactide formed instep (d) to form a substantially purified lactide by distilling thecrude lactide.
 2. The process of claim 1, wherein the source of lacticacid of step (a) is an aqueous solution of lactic acid and water inconcentrations ranging from about 1% lactic acid to about 99% lacticacid.
 3. The process of claim 1, wherein racemization of the lactic acidis controlled in a range of 0% to 100% by altering residence times inprocess equipment, catalyst levels, temperatures and pressures.
 4. Theprocess for of claim 1, wherein the crude lactide formed in step (d) isa vapor, said vapor being subsequently partially condensed to removevolatile contaminants to form a condensed partially purified liquidlactide, the condensed partially purified liquid lactide then beingpurified as in step (e).
 5. The process of claim 1, wherein the sourceof lactic acid for step (a) contains impurities which include but arenot limited to color bodies, carbohydrates, proteins, amino acids,salts, metal ions, or other carboxylic acids.
 6. The process of claim 1,wherein the yield of lactide is maximized by recycling streamscontaining recoverable lactic acid, lactide or oligomers and polymersthereof.
 7. The process of claim 11, wherein the crude lactide formed instep (d) is generated in a reactor under conditions of elevatedtemperature and reduced pressure.
 8. A process for the continuousconversion of a crude lactic acid feed in a hydroxylic medium to asubstantially purified lactide, said process comprising the steps of:a)providing a source of lactic acid in a hydroxylic medium; b)concentrating the lactic acid in the hydroxylic medium by evaporating asubstantial portion of the hydroxylic medium to form a concentratedlactic acid solution; c) polymerizing lactic acid in the concentratedlactic acid solution of step (b) by further evaporation of thehydroxylic medium to form polylactic acid molecules having an averagemolecular weight of between about 100 and about 5000; d) forming a crudelactide in the presence of catalyst means for catalyzing thedepolymerization of the polylactic acid molecules to form lactidemolecules; and e) purifying the crude lactide formed in step (d) to forma substantially purified lactide by distilling the crude lactide.
 9. Theprocess of claim 8, wherein the source of lactic acid of step (a) is ahydroxylic solution of lactic acid and a hydroxylic medium inconcentrations ranging from about 1% lactic acid to about 99% lacticacid.
 10. The process of claim 8, wherein racemization of the lacticacid is controlled in a range of 0% to 100% by altering residence timesin process equipment, catalyst levels, temperatures and pressures. 11.The process of claim 8, wherein the crude lactide formed in step (d) isa vapor being subsequently partially condensed to remove volatilecontaminants to form a condensed partially purified liquid lactide, thecondensed partially purified liquid lactide then being purified as instep (e).
 12. The process of claim 8, wherein the source of lactic acidfor step (a) contains impurities which include but are not limited tocolor bodies, carbohydrates, proteins, amino acids, salts, metal ions,or other carboxylic acids.
 13. The process of claim 8, wherein the yieldof lactide is maximized by recycling streams containing recoverablelactic acid, lactide or oligomers and polymers thereof.
 14. The processof claim 8, wherein the crude lactide formed in step (d) is generated ina reactor under conditions of elevated temperature and reduced pressure.